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The nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We show that NSD1 knockdown alters erythroid clonogenic growth of human CD34 + hematopoietic cells. Ablation of Nsd1 in the hematopoietic system of mice induces a transplantable erythroleukemia. In vitro differentiation of Nsd1 −/− erythroblasts is majorly impaired despite abundant expression of GATA1, the transcriptional master regulator of erythropoiesis, and associated with an impaired activation of GATA1-induced targets. Retroviral expression of wildtype NSD1, but not a catalytically-inactive NSD1 N1918Q SET-domain mutant induces terminal maturation of Nsd1 −/− erythroblasts. Despite similar GATA1 protein levels, exogenous NSD1 but not NSD N1918Q significantly increases the occupancy of GATA1 at target genes and their expression. Notably, exogenous NSD1 reduces the association of GATA1 with the co-repressor SKI, and knockdown of SKI induces differentiation of Nsd1 −/− erythroblasts. Collectively, we identify the NSD1 methyltransferase as a regulator of GATA1-controlled erythroid differentiation and leukemogenesis. Loss of function mutations of NSD1 occur in blood cancers. Here, the authors report that NSD1 loss blocks erythroid differentiation which leads to an erythroleukemia-like disease in mice by impairing GATA1-induced target gene activation.

Plague is a deadly zoonosis that still poses a threat in many regions of the world. We combined epidemiologic, host, and vector surveillance data collected during 1961-1980 from the Araripe Plateau focus in northeastern Brazil with ecologic, geoclimatic, and Yersinia pestis genomic information to elucidate how these factors interplay in plague activity. We identified well-delimited plague hotspots showing elevated plague risk in low-altitude areas near the foothills of the plateau's concave sectors. Those locations exhibited distinct precipitation and vegetation coverage patterns compared with the surrounding areas. We noted a seasonal effect on plague activity, and human cases linearly correlated with precipitation and rodent and flea Y. pestis positivity rates. Genomic characterization of Y. pestis strains revealed a foundational strain capable of evolving into distinct genetic variants, each linked to temporally and spatially constrained plague outbreaks. These data could identify risk areas and improve surveillance in other plague foci within the Caatinga biome.

The nasal epithelium is an initial site for SARS-CoV-2 infection, responsible for the ongoing COVID-19 pandemic. However, the pathogenicity and morphological impact of SARS-CoV-2 on the nasopharynx cells from symptomatic patients with different viral loads remain poorly understood. Here, we investigated the ultrastructure of nasal cells obtained from individuals at distinct disease days and with high and low SARS-CoV-2 loads. Squamous and ciliated cells were the main cells observed in SARS-CoV-2 negative samples. We identified virus-like particles (VLPs) and replication organelles (RO)-like structures in the squamous cells from high viral load samples after 3- and 4-days of symptoms. Ultrastructural changes were found in those cells, such as the loss of microvilli and primary cilium, the increase of multivesicular bodies and autophagosomes, and signs of cell death. No ciliated cells were found in those samples. Squamous cells from low viral load sample after 5 days of symptoms showed few microvilli and no primary cilium. VLPs and RO-like structures were found in the ciliated cells only. No ultrastructural alterations were seen in the cells from low viral load individuals after 10- and 14-days of symptoms. Our results shed light on the ultrastructural effects of SARS-CoV-2 infection on the human nasopharyngeal cells. Competing Interest Statement The authors have declared no competing interest.

Key message We propose an “enviromics” prediction model for recommending cultivars based on thematic maps aimed at decision-makers. Parsimonious methods that capture genotype-by-environment interaction (GEI) in multi-environment trials (MET) are important in breeding programs. Understanding the causes and factors of GEI allows the utilization of genotype adaptations in the target population of environments through environmental features and factor-analytic (FA) models. Here, we present a novel predictive breeding approach called GIS-FA, which integrates geographic information systems (GIS) techniques, FA models, partial least squares (PLS) regression, and enviromics to predict phenotypic performance in untested environments. The GIS-FA approach enables: (i) the prediction of the phenotypic performance of tested genotypes in untested environments, (ii) the selection of the best-ranking genotypes based on their overall performance and stability using the FA selection tools, and (iii) the creation of thematic maps showing overall or pairwise performance and stability for decision-making. We exemplify the usage of the GIS-FA approach using two datasets of rice [ Oryza sativa (L.)] and soybean [ Glycine max (L.) Merr.] in MET spread over tropical areas. In summary, our novel predictive method allows the identification of new breeding scenarios by pinpointing groups of environments where genotypes demonstrate superior predicted performance. It also facilitates and optimizes cultivar recommendations by utilizing thematic maps.

Toxoplasmosis is an important zoonotic disease caused by the parasite Toxoplasma gondii and is especially fatal for neotropical primates. In Brazil, the Ministry of Health is responsible for national epizootic surveillance, but some diseases are still neglected. Here, we present an integrated investigation of an outbreak that occurred during the first year of the COVID-19 pandemic among eleven neotropical primates housed at a primatology center in Brazil. After presenting non-specific clinical signs, all animals died within four days. A wide range of pathogens were evaluated, and we successfully identified T. gondii as the causative agent within four days after necropsies. The liver was the most affected organ, presenting hemorrhage and hepatocellular necrosis. Tachyzoites and bradyzoite cysts were observed in histological examinations and immunohistochemistry in different organs; in addition, parasitic DNA was detected through PCR in blood samples from all specimens evaluated. A high prevalence of Escherichia coli was also observed, indicating sepsis. This case highlights some of the obstacles faced by the current Brazilian surveillance system. A diagnosis was obtained through the integrated action of researchers since investigation for toxoplasmosis is currently absent in national guidelines. An interdisciplinary investigation could be a possible model for future epizootic investigations in animals.

Purpose To investigate the effects of a single dose of juice on physical performance, oxidative stress, inflammation and muscle damage in runners. Methods Fourteen recreational male runners (39 ± 9 years, V O 2peak  = 55.9 ± 6.5 ml/kg/min) performed two running tests to exhaustion at 80% of V O 2max after ingesting grape juice or a placebo drink (10 ml/kg/day) randomly. Blood samples were taken before and 2 h after supplementation and immediately after running to analyze total antioxidant capacity (TAC), malondialdehyde (MDA), alpha-1 acid glycoprotein (A1GPA), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK) and lactate dehydrogenase (LDH). Results The participants ran for an average of 59.2 ± 27.8 min until exhaustion in the placebo group and for 68.4 ± 29.7 min until exhaustion in the grape juice intake group, which was a significantly longer time ( p  = 0.008). This improvement in physical performance was accompanied by a 43.6% increase in TAC ( p  = 0.000) at the post-exercise timepoint compared to the level at baseline. MDA, A1GPA, hs-CRP, CK, and LDH did not exhibit changes. In contrast, no significant change in any variable was observed after consuming the placebo drink. Conclusion The single-dose intake of purple grape juice demonstrated an ergogenic effect in recreational runners by increasing run time to exhaustion and increasing antioxidant activity.

The COVID-19 pandemic posed a worldwide challenge, leading to radical changes in surgical services. The primary objective of the study was to assess the impact of COVID-19 on elective and emergency surgeries in a Brazilian metropolitan area. The secondary objective was to compare the postoperative hospital mortality before and during the pandemic. Time-series cohort study including data of all patients admitted for elective or emergency surgery at the hospitals in the Public Health System of Federal District, Brazil, between March 2018 and February 2022, using data extracted from the Hospital Information System of Brazilian Ministry of Health (SIH/DATASUS) on September 30, 2022. A causal impact analysis was used to evaluate the impact of COVID-19 on elective and emergency surgeries and hospital mortality. There were 174,473 surgeries during the study period. There was a reduction in overall (absolute effect per week: -227.5; 95% CI: -307.0 to -149.0), elective (absolute effect per week: -170.9; 95% CI: -232.8 to -112.0), and emergency (absolute effect per week: -57.7; 95% CI: -87.5 to -27.7) surgeries during the COVID-19 period. Comparing the surgeries performed before and after the COVID-19 onset, there was an increase in emergency surgeries (53.0% vs 68.8%, P < 0.001) and no significant hospital length of stay (P = 0.112). The effect of the COVID-19 pandemic on postoperative hospital mortality was not statistically significant (absolute effect per week: 2.1, 95% CI: -0.01 to 4.2). Our study showed a reduction in elective and emergency surgeries during the COVID-19 pandemic, possibly due to disruptions in surgical services. These findings highlight that it is crucial to implement effective strategies to prevent the accumulation of surgical waiting lists in times of crisis and improve outcomes for surgical patients.

The article A single dose of purple grape juice improves physical performance and antioxidant activity in runners.

Stem cells derived from adipose tissue (ADSC) have been used in cell therapy as an alternative to treat chronic and degenerative diseases. Using biomedical and image trials to track the cells when infused in the target tissue is essential to control cell migration and adhesion. The objective of the present study was to label and assess the adhesion of goat adipose tissue-derived stem cells (g-ADSC) after cell infusion in animal models by tracking luminescent intracytoplasmatic nanocrystals. The cells were labeled by using Qdots. The g-ADSCs infused with nanocrystal were prepared either fresh or fixed and further visualized under a fluorescence microscope. The labeled cells were infused in the goat mammary glands and mouse testicles and kidneys via tail vein injection. Thirty days after cell infusion, biopsy was carried out for analyses. The g-ADSC cultures were presented with high cellularity and fibroblast morphology, even after infusion of the nanocrystals. It was possible, by processing in paraffin and under fluorescence microscopy, demonstrating the success of the labeling in the long term. Freezing mammary gland biopsies in liquid NO2 did not alter the quality of labeling with Qdots. Therefore, g-ADSCs can be labeled with intracytoplasmatic nanocrystals (Qdots) enabling their in vitro and ex vivo tracking.

Background We examined the influence of superoxide dismutase 3 (SOD3) Arg213Gly and Peroxisome Proliferator-Activated α-Receptor (PPARα) 7G/C polymorphisms to a single dose of purple grape juice supplementation on time-to-exhaustion running test, redox balance and muscle damage in recreational runners. Methods Forty-seven male recreational runners performed a running test until exhaustion after supplementation with grape juice or a control drink. Serum total antioxidant capacity (TAC), malondialdehyde (MDA), plasma nitrite (NO), creatine kinase (CK) and lactate dehydrogenase (LDH) were measured pre and post exercise. Also, polymorphisms were analyzed in DNA extracted from the oral mucosa. Results Grape juice improved the time-to-exhaustion. When analyzed by genotype, the recreational runners with GG+CG genotypes of the SOD3 gene had greater time-to-exhaustion than the CC genotype, but was no different for the PAPRα gene. A slight difference was noted in TAC, since the CC genotype of the SOD3 gene showed higher TAC values in the post-exercise compared to the baseline and with pre-exercise, but these values did not increase compared to the CG+GG group, respectively. The SOD3 and PPARα genes were similar at all times for the other biochemical variables. Conclusion The ergogenic effect of grape juice was genotype-dependent for SOD3 Arg213Gly. However, biochemical redox balance markers did not explain this difference.